title: Use of weekly, low dose, high frequency ultrasound for hard to heal venous leg ulcers: the VenUS III randomised controlled trial.
abstract: OBJECTIVE
  To assess the clinical effectiveness of weekly delivery of low dose, high frequency therapeutic ultrasound in conjunction with standard care for hard to heal venous leg ulcers.
  
  
  METHODS
  Multicentre, pragmatic, two arm randomised controlled trial.
  
  
  METHODS
  Community and district nurse led services, community leg ulcer clinics, and hospital outpatient leg ulcer clinics in 12 urban and rural settings (11 in the United Kingdom and one in the Republic of Ireland).
  
  
  METHODS
  337 patients with at least one venous leg ulcer of >6 months' duration or >5 cm(2) area and an ankle brachial pressure index of ≥ 0.8.
  
  
  METHODS
  Weekly administration of low dose, high frequency ultrasound therapy (0.5 W/cm(2), 1 MHz, pulsed pattern of 1:4) for up to 12 weeks plus standard care compared with standard care alone.
  
  
  METHODS
  Primary outcome was time to healing of the largest eligible leg ulcer. Secondary outcomes were proportion of patients healed by 12 months, percentage and absolute change in ulcer size, proportion of time participants were ulcer-free, health related quality of life, and adverse events.
  
  
  RESULTS
  The two groups showed no significant difference in the time to healing of the reference leg ulcer (log rank test, P=0.61). After adjustment for baseline ulcer area, baseline ulcer duration, use of compression bandaging, and study centre, there was still no evidence of a difference in time to healing (hazard ratio 0.99 (95% confidence interval 0.70 to 1.40), P=0.97). The median time to healing of the reference leg ulcer was inestimable. There was no significant difference between groups in the proportion of participants with all ulcers healed by 12 months (72/168 in ultrasound group v 78/169 in standard care group, P=0.39 for Fisher's exact test) nor in the change in ulcer size at four weeks by treatment group (model estimate 0.05 (95% CI -0.09 to 0.19)). There was no difference in time to complete healing of all ulcers (log rank test, P=0.61), with median time to healing of 328 days (95% CI 235 to inestimable) with standard care and 365 days (224 days to inestimable) with ultrasound. There was no evidence of a difference in rates of recurrence of healed ulcers (17/31 with ultrasound v 14/31 with standard care, P=0.68 for Fisher's exact test). There was no difference between the two groups in health related quality of life, both for the physical component score (model estimate 0.69 (-1.79 to 3.08)) and the mental component score (model estimate -0.93 (-3.30 to 1.44)), but there were significantly more adverse events in the ultrasound group (model estimate 0.30 (0.01 to 0.60)). There was a significant relation between time to ulcer healing and baseline ulcer area (hazard ratio 0.64 (0.55 to 0.75)) and baseline ulcer duration (hazard ratio 0.59 (0.50 to 0.71)), with larger and older ulcers taking longer to heal. In addition, those centres with high recruitment rates had the highest healing rates.
  
  
  CONCLUSIONS
  Low dose, high frequency ultrasound administered weekly for 12 weeks during dressing changes in addition to standard care did not increase ulcer healing rates, affect quality of life, or reduce ulcer recurrence. Trial registration ISRCTN21175670 and National Research Register N0484162339.
authors.affiliation: Department of Health Sciences, University of York, UK.
authors.forename: Judith M
authors.initials: JM
authors.lastname: Watson
authors.forename: Arthur R
authors.initials: AR
authors.lastname: Kang'ombe
authors.forename: Marta O
authors.initials: MO
authors.lastname: Soares
authors.forename: Ling-Hsiang
authors.initials: LH
authors.lastname: Chuang
authors.forename: Gill
authors.initials: G
authors.lastname: Worthy
authors.forename: J Martin
authors.initials: JM
authors.lastname: Bland
authors.forename: Cynthia
authors.initials: C
authors.lastname: Iglesias
authors.forename: Nicky
authors.initials: N
authors.lastname: Cullum
authors.forename: David
authors.initials: D
authors.lastname: Torgerson
authors.forename: E Andrea
authors.initials: EA
authors.lastname: Nelson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D057086:High-Intensity Focused Ultrasound Ablation / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D007494:Ireland; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055502:Secondary Prevention; D016896:Treatment Outcome; D006113:United Kingdom; D014647:Varicose Ulcer / Q000503:physiopathology / Q000628:therapy*; D014945:Wound Healing / Q000502:physiology; D055815:Young Adult